Hnrnph2-flox Mouse

Hnrnph2, a member of the HNRNPF/H family of heterogeneous nuclear RNA proteins, is a critical regulator of RNA maturation, with functions including regulating splicing, 5' capping, 3' polyadenylation of RNAs, and RNA export [3]. It typically binds RNA sequences enriched with guanine residues.

Mutations in Hnrnph2 cause an X-linked neurodevelopmental disorder. Over 90% of patients have a missense mutation within or adjacent to the nuclear localization signal of hnRNPH2, which reduces its interaction with the nuclear transport receptor Kapβ2, leading to cytoplasmic accumulation [1,2]. Knockin mouse models with human-equivalent mutations recapitulate clinical features of the human disorder, such as reduced survival in male mice, impaired motor and cognitive functions, and increased susceptibility to audiogenic seizures [1]. In contrast, Hnrnph2-KO mice show no detectable phenotypes, likely due to upregulated expression of Hnrnph1, a paralog of Hnrnph2, which may counteract the loss of hnRNPH2 [1].

In summary, Hnrnph2 is crucial for RNA-related functions. Mouse models, especially the knockin and KO models, have been instrumental in understanding Hnrnph2-related neurodevelopmental disorders, suggesting that the disorder may be due to a toxic gain of function or a complex loss of Hnrnph2 function with impaired compensation by Hnrnph1 [1].